姜黄素纳米晶注射液的制备及体内外性质评价

王荣荣; 孙文军; 刘江伟; 郑爱萍; 张慧; 吕立勋

doi:10.11665/j.issn.1000-5048.20220108

姜黄素纳米晶注射液的制备及体内外性质评价

1.
华北理工大学，唐山 063210
2.
军事科学院军事医学研究院毒物药物研究所，北京 100850
3.
新疆军区总医院，乌鲁木齐 830000

基金项目: 国家自然科学基金资助项目（No.81573357）；国家“重大新药创制”科技重大专项资助项目（No.2018ZX09721003-007）

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出版历程
- 收稿日期: 2021-09-12
- 修回日期: 2022-01-09
- 刊出日期: 2022-02-24

Preparation of curcumin nanocrystalline injection and evaluation of its in vivo and in vitro properties

1.
North China University of Science and Technology, Tangshan 063210
2.
China Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Academy of Military Sciences, Beijing100850, China
3.
General Hospital of Xinjiang Military Region, Urumqi 830000, China

Funds: This study was supported by the National Natural Science Foundation of China (No.81573357);and China National Key Hi-Tech Innovation Project for the R&D of Novel Drugs (No.2018ZX09721003-007)

摘要

摘要: 通过优化姜黄素纳米晶注射液（curcumin nanocrystalline injection）处方及制备工艺，进而提高姜黄素溶出速率及体内生物利用度。采用介质研磨法制备姜黄素纳米晶，以粒径为评价指标，采用Box-Behnken实验设计优化其处方及制备工艺，并对其进行理化性质表征。此外，通过桨法对不同粒径药物溶出进行考察，并研究大鼠体内药代动力学研究。实验结果表明，通过Box-Behnken实验设计得到最优处方和工艺，获得平均粒径为223.1 nm且均一的姜黄素纳米晶。X射线衍射分析和差示扫描量热法测定结果表明，其制备过程中晶型稳定。不同粒径体外溶出实验表明其粒径越小溶出速率越快，溶出程度越高。大鼠体内药代动力学研究显示，姜黄素纳米晶注射液c_max和AUC_0-∞分别是姜黄素原料药的4.9和4.1倍。综上，本研究所开发的姜黄素纳米晶注射液，制备工艺稳定，并且能够显著提高药物溶出速率和生物利用度，为姜黄素制剂研究提供了新的思路。
- 姜黄素 /
- 纳米晶 /
- 工艺优化 /
- Box-Behnken设计 /
- 药代动力学
Abstract: In this study, the formulation and preparation process of curcumin nanocrystalline injection were optimized to improve curcumin dissolution rate and bioavailability in vivo.Media grinding method was used to prepare curcumin nanocrystals, and the particle size was used as the evaluation index.The Box-Behnken experimental design was used to optimize its formulation and preparation process, and to characterize its physical and chemical properties.In addition, the dissolution of nanocrystal with different particle sizes was investigated by the paddle method, and the pharmacokinetics in rats were studied.The experimental results showed that the optimal formula and process were obtained through Box-Behnken experimental design, and that uniform curcumin nanocrystals with an average particle size of 223.1 nm were obtained.The results of X-ray diffraction and differential scanning calorimetry analysis showed that the crystal form was stable during the preparation of nanocrystals. In vitro dissolution experiments with different particle sizes showed that the dissolution rate and the degree of dissolution would increase if the particle size was smaller.Pharmacokinetic studies in rats showed that c_maxand AUC_0-∞ of curcumin nanocrystal injection were 4.9 and 4.1 times that of curcumin raw materials, respectively.In summary, the curcumin nanocrystal injection developed in this research have a stable preparation process and can significantly improve the dissolution rate and bioavailability of the drug, which provides some ideas for the research on curcumin preparation.
- curcumin /
- nanocrystalline /
- process optimization /
- Box-Behnken design /
- pharmacokinetics

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